A. Field of the Invention
The present invention relates to compositions and methods for the prevention and treatment of renal damage. In particular, the invention relates to administration of novel therapeutics to subjects in order to prevent or treat renal degeneration or damage. These novel therapeutics include antibodies, peptides, and small molecules based upon the WISE/SOST family of proteins.
B. Background of the Invention
The mammalian renal system serves primary roles both in the removal of catabolic waste products from the bloodstream and in the maintenance of fluid and electrolyte balances in the body. Renal failures are, therefore, life-threatening conditions in which the build-up of catabolites and other toxins, and/or the development of significant imbalances in electrolytes or fluids, may lead to the failure of other major organs systems and death. Chronic renal failure is a debilitating and life-threatening disease for which no adequate treatment exists.
Tubular damage and interstitial fibrosis are the final common pathways leading to end stage renal disease. Irrespective of the nature of the initial renal injury, the degree of tubular damage parallels the impairment of renal function. Once nephronic degeneration or tubular damage is established, it cannot be reversed or repaired by currently available treatment, and renal function deteriorates to renal failure, which is often life threatening. Renal damage and failure can only be managed through dialysis or organ transplantation.
Dialysis dependency is one of the leading causes of morbidity and mortality in the world. Despite advancement in understanding the pathophysiology of renal diseases, the incidence of end-stage renal disease is increasing. Approximately 600 patients per million receive chronic dialysis each year in the United States, at an average cost approaching $60,000-$80,000 per patient per year. Of the new cases of end-stage renal disease each year, approximately 28-33% are due to diabetic nephropathy (or diabetic glomerulopathy or diabetic renal hypertrophy), 24-29% are due to hypertensive nephrosclerosis (or hypertensive glomeruloscierosis), and 15-22% are due to glomerulonephritis. The 5-year survival rate for all chronic dialysis patients is approximately 40%, but for patients over 65, the rate drops to approximately 20%.
A need remains, therefore, for treatments that will prevent the progressive loss of renal function which has caused almost two hundred thousand patients in the United States alone to become dependent upon chronic dialysis, and which results in the premature deaths of tens of thousands each year.